Female Infertility Caused by Mutations in the Oocyte-Specific Translational Repressor PATL2

• Published in: American journal of human genetics 2017-10, Vol.101 (4), p.603-608
• Main Authors: Maddirevula, Sateesh, Coskun, Serdar, Alhassan, Saad, Elnour, Atif, Alsaif, Hessa S., Ibrahim, Niema, Abdulwahab, Firdous, Arold, Stefan T., Alkuraya, Fowzan S.
• Format: Article
• Language: English
• Subjects: Adult; Cell Differentiation; DNA-Binding Proteins - genetics; Female; Fertilization in Vitro; GVBD; Humans; Infertility, Female - genetics; Infertility, Female - pathology; IVF; Male; maturation arrest; Meiosis; Mutation; Oocytes - metabolism; Oocytes - pathology; P100; PAT1A; Pedigree; Phenotype; Pregnancy
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1016/j.ajhg.2017.08.009

Infertility is a relatively common disorder of the reproductive system and remains unexplained in many cases. In vitro fertilization techniques have uncovered previously unrecognized infertility phenotypes, including oocyte maturation arrest, the molecular etiology of which remains largely unknown. We report two families affected by female-limited infertility caused by oocyte maturation failure. Positional mapping and whole-exome sequencing revealed two homozygous, likely deleterious variants in PATL2, each of which fully segregates with the phenotype within the respective family. PATL2 encodes a highly conserved oocyte-specific mRNP repressor of translation. Previous data have shown the strict requirement for PATL2 in oocyte-maturation in model organisms. Data gathered from the families in this study suggest that the role of PATL2 is conserved in humans and expand our knowledge of the factors that are necessary for female meiosis.